The main barrier to delivery of drugs through the skin is the stratum corneum, which is a tough outer layer of dead skin cells. Drugs may be delivered using microneedles which may be hollow to provide a channel for delivery of a fluid drug through the stratum corneum or they may be solid and simply coated with the drug for delivery. Some suitable drug formulations can alternatively be formed into solid microneedles made of the drug formulation itself, which can penetrate the stratum corneum and then diffuse into the body. In the case of microneedles the inertia created by fluid flow through the bores of the needles, or the high temperature processing required where drug is encapsulated in polymers, or the large pressures applied to compress the drug itself into needles can affect the stability and integrity of the drug, in particular if the drug is a protein, whereby agglomeration, fragmentation, unfolding, and physical and chemical degradation can result from such processing conditions.
Alternatively, a device comprising solid microneedles may be used to disrupt the stratum corneum and/or to create pores through it in order to enhance its permeability to a drug that is subsequently applied to the surface of the skin, for example in the form of a gel or in a patch. However, because the needles only perforate a small proportion of the surface area of skin being treated, a majority of the subsequently applied drug formulation does not enter the pores but remains on the surface of the skin. Published patent application WO 2012/035334 describes devices for transdermal drug delivery which overcome these impediments by first creating at least one hole in the skin using the needles, followed by the insertion of the drug through the hole/pore that has been created. The patent describes methods and devices for achieving this by first creating the hole in the skin, followed by removal of the needle, and subsequent insertion of the drug through the pore. It also describes the insertion of the drug whilst the needle still remains inside the skin by inserting the drug formulation using a carrier, alongside the needle.